The present invention relates to methods and medical devices for the controlled, localized delivery of bioactive agents within a body.
The systemic administration of drug agents, such as by intravenous means, treats the body as a whole even though the disease to be treated may be localized. Thus, it has become common to treat a variety of medical conditions by introducing an implantable medical device partly or completely into a body cavity such as the esophagus, trachea, colon, biliary tract, urinary tract, vascular system or other location within a human or veterinary patient. For example, many treatments of the vascular system entail the introduction of a device such as a stent, catheter, balloon, guide wire, cannula or the like. One of the potential drawbacks to conventional drug delivery techniques with the use of these devices being introduced into and manipulated through the vascular system, is that blood vessel walls can be disturbed or injured. Clot formation or thrombosis often results at the injured site, causing stenosis (closure) of the blood vessel.
Another cause of stenosis is vascular disease. Probably the most common disease causing stenosis of blood vessels is atherosclerosis. Atherosclerosis is a condition which commonly affects the coronary arteries, the aorta, the iliofemoral arteries and the carotid arteries.
Many medical devices and therapeutic methods are known for the treatment of atherosclerotic disease. One particular therapy for certain atherosclerotic lesions is percutaneous transluminal coronary angioplasty (PTCA). Another therapy for certain atherosclerotic lesions is percutaneous transluminal angioplasty (PTA). During PTA, a deflated balloon-tipped catheter is inserted in a patient""s artery. The tip of the catheter is advanced to the site of atherosclerotic plaque. Inflation of the balloon xe2x80x9ccracksxe2x80x9d the atherosclerotic plaque and expands the vessel, thereby relieving the stenosis, at least in part.
While PTA presently enjoys wide use, it suffers from two major problems. First, the blood vessel may suffer acute occlusion immediately after or within the initial hour after the dilation procedure. Such occlusion is referred to as xe2x80x9cabrupt closure.xe2x80x9d A second major problem encountered in PTA is the re-narrowing of an artery after an initially successful angioplasty. This re-narrowing is referred to as xe2x80x9crestenosisxe2x80x9d and typically occurs within the first six months after angioplasty. Restenosis is believed to arise through the proliferation and migration of cellular components from the arterial wall, as well as through geometric changes in the arterial wall referred to as xe2x80x9cremodeling.xe2x80x9d
A device such as an intravascular stent including stent grafts and covered stents can be a useful adjunct to PTA, particularly in the case of either acute or threatened closure after angioplasty. The stent is placed in the dilated segment of the artery to mechanically prevent abrupt closure and restenosis. Unfortunately, even when the implantation of the stent is accompanied by aggressive and precise antiplatelet and anticoagulation therapy (typically by systemic administration), the incident of thrombotic vessel closure or other thrombotic complication remains significant, and the prevention of restenosis is not as successful as desired. Furthermore, an undesirable side effect of the systemic antiplatelet and anticoagulation therapy is an increased incidence of bleeding complications, most often at the percutaneous entry site.
Other conditions and diseases are also treatable with stents, catheters, cannulae and other devices inserted into the esophagus, trachea, colon, biliary tract, urinary tract and other locations in the body, or with orthopedic devices, implants, or replacements, for example. One of the drawbacks of conventional means of drug delivery using such devices is the difficulty in effectively delivering the bioactive agent over a short term (that is, the initial hours and days after insertion of the device) as well as over a long term (the weeks and months after insertion of the device). Another difficulty with the conventional use of stents for drug delivery purposes is providing precise control over the delivery rate of the desired bioactive agents, drug agents or other bioactive material. The term xe2x80x9cbioactive agentxe2x80x9d is used herein to mean any agent such as a pharmaceutical agent or drug or other material that has a therapeutic effect.
It is desirable to develop devices and methods for reliably delivering suitable amounts of therapeutic agents, drugs or bioactive materials directly into a body portion during or following a medical procedure, so as to treat or prevent such conditions and diseases, for example, to prevent abrupt closure and/or restenosis of a body portion such as a passage, lumen or blood vessel.
In view of the potential drawbacks to conventional drug delivery techniques, there exists a need for a device, method and method of manufacture which enable a controlled localized delivery of active agents, drug agents or bioactive material to target locations within a body.
The foregoing problems are solved and a technical advance is achieved in an illustrative vascular stent or other implantable medical device that provides a controlled release of at least one bioactive agent into the vascular or other system, or other location in the body, into which the stent or medical device is positioned. In one aspect, the present invention provides an implantable medical device having a structure adapted for introduction into a patient, e.g., a stent, coil, catheter, etc. The implantable medical device of the invention comprises at least one composite layer of a bioactive agent and a polymer material and at least one barrier layer positioned over the composite layer or layers. The barrier layer has a thickness adequate to provide a controlled release of the bioactive material. The barrier layer is applied to the medical device by a low energy plasma polymerization process which comprises placing the composite covered medical device in a plasma chamber and introducing at least one monomer gas into the chamber to form at least one barrier layer. In another embodiment of the invention, the barrier layer comprises at least one bioactive agent.
In another aspect, the present invention includes a method for the localized delivery of a bioactive agent to a target location within the body. The method includes the first steps of providing a medical device having a structure adapted for introduction into a patient wherein the structure is composed of a base material, at least one composite layer of a bioactive agent and a polymer material applied to the base material. At least one barrier layer is positioned over the composite layer and applied to the composite layer by a low energy plasma polymerization process. The barrier layer has a thickness adequate to provide a controlled release of the bioactive material. The plasma polymerization process includes the steps of placing the composite covered device in a plasma chamber and introducing at least one monomer gas into the plasma chamber to form at least one barrier layer on the outer surface of the composite covered device. The method for localized delivery of a bioactive material includes a second step of delivering the implantable medical device to the target location.